CD90+ Stromal Cells are Non-Professional Innate Immune Effectors of the Human Colonic Mucosa

Benjamin M J Owens,Michael Dudek,Alison Simmons,Alice Mayer,Philip Allan,Tessa A M Steevels,David Walcott,Mei-Yi Sun

doi:10.3389/fimmu.2013.00307

Abstract

Immune responses at the intestinal mucosa must allow for host protection whilst simultaneously avoiding inappropriate inflammation. Although much work has focused on the innate immune functionality of hematopoietic immune cells, non-hematopoietic cell populations – including epithelial and stromal cells – are now recognized as playing a key role in innate defense at this site. In this study we examined the innate immune capacity of primary human intestinal stromal cells (iSCs). CD90+ iSCs isolated from human colonic mucosa expressed a wide array of innate immune receptors and functionally responded to stimulation with bacterial ligands. iSCs also sensed infection with live Salmonella typhimurium, rapidly expressing IL-1 family cytokines via a RIPK2/p38MAPK-dependent signaling process. In addition to responding to innate immune triggers, primary iSCs exhibited a capacity for bacterial uptake, phagocytosis, and antigen processing, although to a lesser extent than professional APCs. Thus CD90+ iSCs represent an abundant population of “non-professional” innate immune effector cells of the human colonic mucosa and likely play an important adjunctive role in host defense and immune regulation at this site.

Highlights

Emerging data suggests that non-hematopoietic stromal cells of the intestine exhibit a wider array of immunological functions than has been hitherto attributed to them
In contrast NOD2 was expressed at significantly lower levels in intestinal stromal cells (iSCs) than monocytes (0.06 ± 0.04 vs. 4.80 ± 1.26 arbitrary units (AU), p < 0.001) and TLR4 expression was lower in iSCs (1.25 ± 0.82 vs. 3.61 ± 1.43, p < 0.01) (Figure 1B). iSCs expressed TLR5, albeit at lower levels than monocytes (Figure 1B). iSCs expressed mRNA for the inflammasome-linked sensors NLRP1 and NLRP3 (Figure 1C), expression was significantly lower compared to monocytes
Previous data has indicated that murine stromal cells express abundant levels of NLRP6 [11], expression of NLRP6 mRNA in human iSCs was very low and not detectable in cells isolated from all patients

Summary

Introduction

Emerging data suggests that non-hematopoietic stromal cells of the intestine exhibit a wider array of immunological functions than has been hitherto attributed to them This includes the production of and response to cytokines, functional interactions with hematopoietic immune cells, the regulation of immune cell localization, and cell-intrinsic innate immune functions [1, 2]. Consistent with this, iSCs internalize and respond rapidly to in vitro infection with the flagellated bacterium Salmonella typhimurium, increasing their expression of IL-1β and IL-33 at both the mRNA and protein level, with this sensing dependent on RIPK2/p38MAPK signaling In addition to these potent cell-intrinsic innate sensing responses, primary iSCs had some phagocytic and antigen-processing potential, this was limited when compared to professional APCs. we identify CD90+ stromal cells as“non-professional”innate immune effector cells of the human colonic mucosa

Methods

Results

Conclusion